Rhodanine beta-substituted propionic acid



Patented Aug. 7, 1951 ACID T mas L. Gresham and Forrest Shaver, kron,Ohio, assignors to The B. F. Goodrich Company, New York, N. Y., acorporation of No Drawing. Application July 1949, Serial No. 103,168

This invention relates to the preparation of beta-substituted carboxylicacids, particularly propionic acids, and is especiallyconcerned with thepreparation of such compoundsby the reaction of beta-lactones withcertai-n nitrogen, sulfur and oxygen-containing heterocyclic compoundssuch as rhodanine. v

It is disclosed in U. .S. P-atent 2,356,459 to Frederick E. Kiingthatbeta-lactones, that is, lactones or inner esters of beta-'hydroxycarboxylic acids may be obtainedin good yields by the reaction of aketene with an aldehyde or ketone. In this manner beta-propiolactone(also .called' hydracrylic acidlactone) which has the structure I iseconomically obtained from .ketene and formaldehyde;

We have now iscovered that beta-propiolactone, and also the othersaturated aliphatic betalactones, will react with nitrogen, sulfur andoxygen-containing heterocyclic compounds containing the structure N. Ij.

wherein B represents a radical containing' from three to four cyclicatoms from two to three of which are carbon and one of which is nitrogenor sulfur, and having from one to three 'oxo atoms (0:) attached tocyclic carbon atoms, to

produce beta-substituted carboxylic acids. The

equation for this reaction is believed to be represented as follows:

i 1 Claim. (01. 260-30611) "iaif Examples of nitrogen, sulfur andoxygen-com taining heterocyclic compounds of the class described are thefollowing:

O=C---.NH

s A Rhodanine Thiohydantoin "b e-inn Hz' ='S Oat-I'm Thiobarbituric acido=o IH 0:2: =s o:e '1qri 2-thioalloxan o=o-NH .Hfl at 2-thiono-4-keto-L3'thiazine :No specialconditions for the reaction .arenecessary, the reaction proceeding whenever it' is possible to bring thereactants into effective contact with one another. This is ordinarilyaccomplished by the use of a solvent for the reactants, polar solventsbeing preferred. Since many of the nitrogen, oxygen andsulfur-containing heterocyclic compounds are soluble in water or inaqueous alkaline solutions the use of water or an alkali solution as themedium for the reactants is an especially preferred procedure. In thisevent the beta-substituted acid, being generally insoluble in water, isprecipitated during the reaction or on acidification of the reactionmedium and is thus readily separated from the reaction medium. Otherpolar solvents which dissolve the reactants such as alcohols, organicacids, organic nitriles, and the like, however. may also be used. Thetemperature at which the reaction is efiected is not critical but ispreferably from 0 to C., more preferably from 0 to 50 C. Proportions ofreactants may be varied widely using an excess of either of thereactants if desired, but in general the use of substantiallyequimolecular proportions of the reactants is preferred.

Example 26.6 parts (0.2 mole) of rhodanine and 8.5 parts of sodiumhydroxide are added, to 125 parts of H Water. 14.4 parts (0.2 mole) ofbeta-propiolactone are slowly added to this mixture with constantstirring, the temperature of the reaction mixture being maintained atfrom to C.

After the lactone addition is complete, 0.2 mole of concentratedhydrochloric acid is added to the reaction mixture, whereupon a red oillayer is formed which crystallizes upon standing. The crystallineproduct is then removed by filtering and recrystallized first from awater-ethanol mixture and secondly from chloroform. A yield of acompound melting at 132-133 C. and pos- When the above example isrepeated using thiohydantoin, thiobarbituric acid and thioallantoin inplace of rhodanine'other solid beta-substituted propionic acids aresecured. When the example is repeated using-2-thiono-4-keto-1,B-thiazane and in the absence of alkali, a good yieldof the corresponding beta-substituted propionic acid is secured.

Although beta-propiolactone, the simplest possible beta-lactone, is thepreferred beta-lactone for use in this invention because of its lowcost, its solubility in water and the ease with which the reaction iscarried out, the homologs of betapropiolactone, that is, other saturatedaliphatic beta-lactones such as beta-butyrolactone,betaisobutyrolactone, beta-valerolactone, beta-isovalerolactone,beta-n-caprolactone, alpha-ethylbeta-propiolactone,alpha-isopropyl-beta-propiolactone, alpha-buty1-beta-propiolact0ne,alphaisopropyl-beta-propiolactone, alpha-butyl-betapropiolactone,alpha-methyl-beta-butyrolactone, alpha-ethyl-beta-butyrolactone,beta-methyl- I beta-valerolactone and the like may also be used toproduce other beta-substituted carboxylic acid 11 compounds. All thesebeta-lactones are of the general structure R R a R C Cc=0 l wherein Rishydrogen or a lower alkyl group so that the lactone contains a totalof 3 to 8 carbon atoms. 1

The beta-substituted carboxylic acids obtained hy the reaction describedare generally solid organic compounds which are useful as intermediatesin the preparation of other compounds and for various other purposes. Inmany instances they may be cyclicized to produce heterocyclic nitrogenand sulfur containing compounds. They are also useful in the preparationof insecticidal, fungicidal and physiologically active compositions.

Numerous other modifications and variations in the method of effectingthe reaction and in the materials therein used will be obvious to thoseskilledin the art and are within the spirit and scope of the inventionas defined in the appended claims.

This application is a continuation-in-part of the copending applicationSerial No. 620,661, filed October 5, 1945, now U. S. Patent 2,474,838.

We claim:

The compound of the formula THOMAS L. GRESHAM. FORREST W. SHAVER.

REFERENCES CITED The following references are of record in the file ofthis patent:

UNITED STATES PATENTS Number Name Date 2,099,374 Schwarz Nov. 16, 19372,407,138 Clifford Sept. 3, 1946 2,483,416 Jansen et al. Oct. 4, 1949Certificate of Correction Patent No. 2,563,034 August 7, 1951 4 THOMASL. GRESHAM ET AL.

It is hereby certified that error appears in the printed specificationof the above numbered patent requiring correction as follows:

Column 1, lines 43 to 46, inclusive, for that portion of the formulareading R R R R -\-O-/C-OH r ad c -rll-on column 3, line 33, in thetable, second column thereof, for C H O S N read O H O S N same table,column 3 thereof, same line, for Foand read F otmd;

and that the said Letters Patent should be read as corrected above, sothat the same may conform to the record of the case in the PatentOffice. Signed and sealed this 12th day of February, A. D. 1952.

THOMAS F. MURPHY,

Assistant Uommz'ssz'oner of Patents.

